Periconceptional environment predicts leukocyte telomere length in a cross-sectional study of 7–9 year old rural Gambian children

Abstract

Early life exposures are important predictors of adult disease risk. Although the underlying mechanisms are largely unknown, telomere maintenance may be involved. This study investigated the relationship between seasonal differences in parental exposures at time of conception and leukocyte telomere length (LTL) in their offspring. LTL was measured in two cohorts of children aged 2 yrs (N = 487) and 7-9 yrs (N = 218). The association between date of conception and LTL was examined using Fourier regression models, adjusted for age, sex, leukocyte cell composition, and other potential confounders. We observed an effect of season in the older children in all models [likelihood ratio test (LRT) χ² 2 = 7.1, p = 0.03; fully adjusted model]. LTL was greatest in children conceived in September (in the rainy season), and smallest in those conceived in March (in the dry season), with an effect size (LTL peaknadir) of 0.60 z-scores. No effect of season was evident in the younger children (LRT χ² 2 = 0.87, p = 0.65). The different results obtained for the two cohorts may reflect a delayed effect of season of conception on postnatal telomere maintenance. Alternatively, they may be explained by unmeasured differences in early life exposures, or the increased telomere attrition rate during infancy. The developmental origins of health and disease (DOHaD) paradigm holds that early life factors are important determinants of disease risk in adult life 1,2. The processes involved in gamete maturation, conception and early embryogenesis appear particularly vulnerable to environmental exposures (reviewed in 3). The biological mechanisms underlying associations between the periconceptional environment and future health remain poorly understood, although persistent epigenetic changes may play a role 4-7. Another molecular process through which the effects of early life factors may exert enduring changes to cellular and organismal phenotypes is the maintenance of telomeres: nucleoprotein structures that protect the ends of linear chromosomes. A potential role for telomere biology in the developmental programming of adult disease is supported by preliminary evidence from both animal and human studies 8-11. Vertebrate telomeres consist of variable numbers of a tandem repeat sequence, (TTAGGG) n , bound to the shelterin protein complex 12. In germ cells and embryonic tissues, telomere length is maintained through the addition of de novo telomeric DNA repeats to the chromosome ends by telomerase. However, this enzyme is generally not active in differentiated cells postnatally. Therefore, in proliferative tissues, telomeres shorten with each cell

Environmental Exposures around Conception: Developmental Pathways Leading to Lifetime Disease Risk

“…Whether and how the altered ME methylation pattern may function in regulating phenotype in offspring is the central question moving forwards, but a strategy to identify associations with gene pathways is feasible, despite the variation in human genotype and other confounders. One mechanism linking the seasonal nature of maternal nutrition at conception in the Gambia with offspring phenotype is telomere length in childhood [36].…”

Prenatal multiple micronutrient-fortified balanced energy-protein supplementation and newborn telomere length and mitochondrial DNA content: a randomized controlled efficacy trial in rural Burkina Faso

“…In conclusion, our results do not indicate that the provision of daily MMNfortified BEP supplements to pregnant females affects newborn TL or mtDNAc. Future randomized interventions should assess the effects of preconception (84) and prenatal nutritional supplementation on absolute TLs and more granular measures of mitochondrial bio-energetic functioning (e.g., oxygen consumption rate, mtDNA mutations and deletions), while larger observational studies might further explore the TLs and mtDNAc of infants born with adverse phenotypes. 1 Values are means ± standard deviation.…”